Chen Wan-Meng, Hu Qing-Yong, Hou Wei, Chen Meng-Wei, Chen Ya-Hui, Tang Jian-Cai
Department of Biochemistry, Institute of Basic Medicine and Forensics Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Oncol Lett. 2023 Aug 28;26(4):443. doi: 10.3892/ol.2023.14030. eCollection 2023 Oct.
Nuclear factor erythroid 2-related factor 3 (Nrf3) is increasingly implicated in multiple types of cancer; however, its function in triple-negative breast cancer (TNBC) remains unclear. This study aimed to examine the role of Nrf3 in TNBC. Compared with adjacent normal tissues, TNBC tissues expressed higher levels of Nrf3, and its expression was negatively correlated with survival time. Additionally, Nrf3 knockdown reduced the proliferation and migration of TNBC cells, whereas overexpression of Nrf3 had the opposite effects and . Moreover, functional enrichment of TNBC cells overexpressing Nrf3 allowed for the identification of numerous genes and pathways that were altered following Nrf3 overexpression. Further study showed that overexpression of Nrf3 activated the PI3K/AKT/mTOR signaling pathway and regulated the expression of proteins associated with epithelial-mesenchymal transition. Nrf3 was found to directly bind to p110α promoter regions, as evidenced by luciferase reporter and chromatin immunoprecipitation assays. Furthermore, PI3K inhibitors partially decreased the proliferation and migration of the Nrf3 overexpressing TNBC cells. In conclusion, Nrf3 enhances cellular proliferation and migration by activating PI3K/AKT/mTOR signaling pathways, highlighting a novel therapeutic target for TNBC.
核因子红细胞2相关因子3（Nrf3）越来越多地与多种癌症相关；然而，其在三阴性乳腺癌（TNBC）中的功能仍不清楚。本研究旨在探讨Nrf3在TNBC中的作用。与相邻正常组织相比，TNBC组织中Nrf3表达水平更高，且其表达与生存时间呈负相关。此外，敲低Nrf3可降低TNBC细胞的增殖和迁移，而Nrf3过表达则产生相反的效果。此外，对过表达Nrf3的TNBC细胞进行功能富集分析，可鉴定出Nrf3过表达后发生改变的众多基因和信号通路。进一步研究表明，Nrf3过表达激活了PI3K/AKT/mTOR信号通路，并调节了与上皮-间质转化相关的蛋白质表达。荧光素酶报告基因和染色质免疫沉淀实验证明，Nrf3可直接结合到p110α启动子区域。此外，PI3K抑制剂可部分降低过表达Nrf3的TNBC细胞的增殖和迁移。总之，Nrf3通过激活PI3K/AKT/mTOR信号通路增强细胞增殖和迁移，为TNBC提供了一个新的治疗靶点。
